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An Entirely Subcutaneous Implantable CardioverterDefibrillator

Gust H. Bardy, M.D., Warren M. Smith, M.B., Margaret A. Hood, M.B., Ian G. Crozier, M.B., Iain C. Melton, M.B., Luc Jordaens, M.D., Ph.D., Dominic Theuns, Ph.D., Robert E. Park, M.B., David J. Wright, M.D., Derek T. Connelly, M.D., Simon P. Fynn, M.D., Francis D. Murgatroyd, M.D., Johannes Sperzel, M.D., Jrg Neuzner, M.D., Stefan G. Spitzer, M.D., Andrey V. Ardashev, M.D., Ph.D., Amo Oduro, M.B., B.S., Lucas Boersma, M.D., Ph.D., Alexander H. Maass, M.D., Isabelle C. Van Gelder, M.D., Ph.D., Arthur A. Wilde, M.D., Ph.D., Pascal F. van Dessel, M.D., Reinoud E. Knops, M.D., Craig S. Barr, M.B., Pierpaolo Lupo, M.D., Riccardo Cappato, M.D., and Andrew A. Grace, M.B., Ph.D.

A bs t r ac t
Background

Implantable cardioverterdefibrillators (ICDs) prevent sudden death from cardiac caus es in selected patients but require the use of transvenous lead systems. To eliminate the need for venous access, we designed and tested an entirely subcutaneous ICD system.
Methods

The authors affiliations are listed in the Appendix. Address reprint requests to Dr. Bardy at the Seattle Institute for Cardiac Research, 10115 NE 24th St., Bellevue, WA 98004, or at gbardy@sicr.org. This article (10.1056/NEJMoa0909545) was published on May 12, 2010, at NEJM.org. N Engl J Med 2010.
Copyright 2010 Massachusetts Medical Society.

First, we conducted two shortterm clinical trials to identify a suitable device con figuration and assess energy requirements. We evaluated four subcutaneous ICD configurations in 78 patients who were candidates for ICD implantation and subse quently tested the best configuration in 49 additional patients to determine the sub cutaneous defibrillation threshold in comparison with that of the standard trans venous ICD. Then we evaluated the longterm use of subcutaneous ICDs in a pilot study, involving 6 patients, which was followed by a trial involving 55 patients.
Results

The best device configuration consisted of a parasternal electrode and a left lateral thoracic pulse generator. This configuration was as effective as a transvenous ICD for terminating induced ventricular fibrillation, albeit with a significantly higher mean (SD) energy requirement (36.619.8 J vs. 11.18.5 J). Among patients who received a permanent subcutaneous ICD, ventricular fibrillation was successfully detected in 100% of 137 induced episodes. Induced ventricular fibrillation was converted twice in 58 of 59 patients (98%) with the delivery of 65J shocks in two consecutive tests. Clinically significant adverse events included two pocket infections and four lead revi sions. After a mean of 101 months, the device had successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia.
Conclusions

In small, nonrandomized studies, an entirely subcutaneous ICD consistently detected and converted ventricular fibrillation induced during electrophysiological testing. The device also successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. (ClinicalTrials.gov numbers, NCT00399217 and NCT00853645.)
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he use of implantable cardioverter defibrillators (ICDs) is an established ther apy for the prevention of death from ven tricular arrhythmia.1-5 However, conventional ICDs rely on transvenous leads for cardiac sensing and defibrillation. Complications of defibrillator im plantation have been associated mainly with transvenous lead insertion and have included pneumothorax, hemothorax, and cardiac tampon ade.6-10 Difficulties in achieving venous access can prolong the procedure and occasionally result in failed ICD implantation.11-13 In the long term, lead failure remains a major limitation in the use of ICDs, despite decades of innovations in lead de sign.12-22 Lead failure either generates inappropri ate shocks or impedes appropriate therapy.20-23 Moreover, failed leads often require removal, a pro cedure that is associated with substantial mor bidity and mortality.24-36 If cardiac pacing is not necessary, there may be a clinical advantage in avoiding the use of transvenous electrodes. In this report, we describe the initial evaluation of an en tirely subcutaneous ICD system designed to avoid the need for the placement of sensing and therapy electrodes within or on the heart.

Me thods
Study Design

to identify the best electrode configuration among those tested for the subcutaneous ICD. Four elec trode configurations were selected on the basis of the use of specific anatomical landmarks: a left lateral pulse generator with an 8cm coil electrode positioned at the left parasternal margin, a left pectoral pulse generator with a 4cm coil elec trode at the left inferior sternum, a left pectoral pulse generator with an 8cm coil electrode curv ing from the left inferior sternum across to the inferior margin of the left sixth rib, and a left lateral pulse generator with a left parasternal 5cm2 oval disk (Fig. 1). A total of 78 patients participated in this trial. Each patient underwent temporary subcutaneous implantation of one or more of the four device configurations evaluated and testing of the defi brillation threshold. The details of the protocol for defibrillationthreshold testing are described in the Supplementary Appendix, available with the full text of this article at NEJM.org. Testing was conducted in an interleaved fashion with the use of a Latin square design; the data were evaluated by means of analysis of variance.38,39 After comple tion of the study, all temporary subcutaneous de vices were explanted, and each patient underwent implantation of a conventional transvenous ICD.
Comparison of Temporary Subcutaneous ICD with Transvenous ICD

We report the results of two shortterm trials of a temporarily inserted subcutaneous ICD electrode system, followed by two trials of longterm sub cutaneous ICD implantation of a fully functional system. All the studies were sponsored by the manufacturer of the subcutaneous ICD, Cameron Health, and were designed by six of the academic investigators. The protocols were approved by the ethics committee at each participating institution and associated national and local regulatory agen cies. All study participants satisfied standard cri teria for ICD implantation37 and provided written informed consent. Study data were collected by all the authors; device data were provided by engineers employed by the sponsor. The original manuscript was written by the first author with review and revi sion by all coauthors. All authors vouch for the accuracy and completeness of the data and the analyses.
Evaluation of Lead Configuration

From April 2004 through June 2005, in a second shortterm trial involving 49 patients, we compared the best of the tested subcutaneous ICD systems in the first shortterm trial (Fig. 1A) with a trans venous ICD system. For each patient, both the subcutaneous and transvenous devices were im planted during the same procedure. Defibrilla tion thresholds were compared after both sys tems were in position and both surgical pockets had been closed. The system that was tested first was selected randomly. The protocol for defibril lationthreshold testing of the subcutaneous ICD was identical to that used in the first shortterm trial, as described in the Supplementary Appen dix. The statistical comparison of the defibrilla tion thresholds for the devices was performed with the use of a paired ttest. After completion of the study, the subcutaneous device was explanted.
Permanent Implantation

From September 2001 through February 2004, we After the two shortterm trials, we performed two conducted the first shortterm defibrillation trial trials of permanent subcutaneous ICD implanta
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A
LGen-S8

B
PGen-S4

PGen-C8

LGen-S5 Disk

Figure 1. Four Configurations of a Subcutaneous Implantable CardioverterDefibrillator. The four lead systems that were tested to select the best of these candidates were a left lateral pulse generator with an 8-cm coil electrode positioned at the left parasternal margin, designated LGen-S8 (Panel A); a left pectoral pulse generator with a left parasternal 4-cm coil electrode at the inferior sternum, designated PGen-S4 (Panel B); a left pectoral pulse generator with an 8-cm coil electrode curving from the left inferior parasternal line across to the inferior margin of the left sixth rib, designated PGen-C8 (Panel C); and a left lateral pulse generator with a left parasternal 5-cm2 oval disk, designated LGen-S5 (Panel D).

tion: a pilot trial involving 6 patients who under went implantation in July 2008 in New Zealand, followed by a trial involving 55 patients who un derwent implantation in New Zealand and Eu rope between December 2008 and February 2009. We identified candidates for subcutaneous ICD implantation among the patients who were re ferred for ICD implantation at each participating center. The inclusion criterion was a class I, IIa,

or IIb indication for ICD therapy.37 Exclusion cri teria were an estimated glomerular filtration rate of less than 30 ml per minute, a requirement for antibradycardia pacing, a history of ventricular tachycardia at rates slower than 170 beats per min ute, and documented ventricular tachycardia known to be reliably terminated with antitachycardia pac ing. The primary end point was successful imme diate conversion of two consecutive episodes of in
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D Pulse generator

Figure 2. Locations of the Components of a Subcutaneous Implantable CardioverterDefibrillator in Situ. The distal and proximal sensing electrodes (D and P, respectively) of the LGen-S8 device are shown, with the left lateral pulse generator and an 8-cm parasternal coil electrode (C).

duced ventricular fibrillation, each with a single 65J shock.

Subcutaneous ICD System

The subcutaneous ICD system that we tested in these studies consists of a 3mm tripolar para sternal electrode (polycarbonate urethane 55D), which is connected to an electrically active pulse generator. The electrode is positioned parallel to and 1 to 2 cm to the left of the sternal midline, and the pulse generator is positioned over the sixth rib between the midaxillary line and the anterior axillary line (Fig. 2). The electrode has an 8cm shocking coil, flanked by two sensing electrodes. The distal sensing electrode is positioned adja cent to the manubriosternal junction, and the proximal sensing electrode is positioned adjacent to the xiphoid process. The insertion of the sub cutaneous ICD is guided exclusively by anatomical landmarks; no fluoroscopy is required. The surgi cal procedure and the devicetesting protocol dur ing implantation are described in the Supplemen tary Appendix. During device operation, the cardiac rhythm is
4

detected by the two sensing electrodes or by either of the sensing electrodes and the pulse generator. The subcutaneous ICD system automatically se lects an appropriate vector for rhythm detection and for avoiding double QRS counting and Twave oversensing. Once signals have been validated as free of noise and double detection, feature analy sis and rate detection are used to sort rhythm type and determine the need for therapy. A condition al discrimination zone incorporating a feature extraction technique can be programmed between rates of 170 and 240 beats per minute to distin guish supraventricular tachycardia from ventric ular tachycardia and avoid inappropriate treatment of the former. Reconfirmation of ventricular tach yarrhythmia follows capacitor charging to avoid the delivery of shocks for nonsustained ventricu lar tachyarrhythmias. Testing of the device during implantation is done with the use of 65J shocks to ensure a margin of safety. However, after the device has been implanted, it delivers only 80J shocks. It can also reverse shock polarity auto matically if the initial shock is not successful. In addition, demand pacing at 50 beats per minute is available for 30 seconds after a shock, with the use of a 200mA biphasic transthoracic pulse. Pac ing is activated only after more than 3.5 seconds of postshock asystole. All device settings are automated except for shock therapy (on/off), pacing after a shock (on/ off), conditional discrimination of supraventricu lar tachycardia (on/off), and the upperrate cutoff for the conditional shock zone (between 170 and 240 beats per minute). Data storage includes pre event electrograms and rhythm markers through event termination. Up to 24 treated episodes can be stored, with up to 120 seconds of data per episode.

R e sult s
Evaluation of Lead Configuration

In the study comparing four lead configurations, the mean (SD) age of the 78 patients was 6111 years (range, 31 to 80), and 72 of the patients were men. The average weight was 82.415.2 kg (range, 53.0 to 143.5 [18234 lb; range, 117 to 316]). The mean ejection fraction was 0.350.14 (range, 0.10 to 0.69). The mean defibrillation thresholds were 32.517.0 J (95% confidence interval [CI], 27.8 to 37.3) for configuration 1, 40.413.7 J (95% CI, 35.4 to 45.4) for configuration 2, 40.114.9 J (95% CI, 33.7 to 46.5) for configuration 3, and 34.312.1 J
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Mean Delivered Energy (J)

(95% CI, 28.8 to 39.8) for configuration 4 (Fig. 3A). The left lateral pulse generator with the 8cm parasternal coil electrode (Fig. 1A) had the low est mean defibrillation threshold, although the differences among the configurations were not significant (P = 0.07 for all comparisons by analy sis of variance).
Temporary Subcutaneous ICD versus Transvenous ICD

A Delivered Energy
100 80 60 40 20 0 32.5 (N=61)

40.4 (N=31)

40.1 (N=23)

In the study comparing the subcutaneous ICD with the transvenous ICD, the mean age of the 49 patients was 6411 years (range, 42 to 79), and 47 of the patients were men. The average weight was 85.312.8 kg (range, 61.0 to 114.0 [18828 lb; range, 134 to 251]). The mean ejection fraction was 0.370.13 (range, 0.19 to 0.70). The mean de fibrillation threshold was 11.18.5 J (95% CI, 8.6 to 13.5) with the transvenous ICD and 36.619.8 J (95% CI, 31.1 to 42.5) with the subcutaneous ICD (P<0.001) (Fig. 3B). The transvenous device in one patient and the subcutaneous device in an other patient failed to terminate induced ventric ular fibrillation at maximum device output. In the patient whose subcutaneous ICD failed defi brillation testing, the parasternal electrode had been incorrectly positioned approximately 6 cm to the left of the sternum, beyond the left lateral margin of the heart.
Permanent Subcutaneous ICD Pilot Study

34.3 (N=21)

LGen-S8

PGen-S4

PGen-C8

LGen-Disk

Configuration

B Defibrillation Threshold
120 100 80 60 40 20 0 Transvenous ICD Subcutaneous ICD

Defibrillation Threshold (J)

Configuration

Six patients requiring ICD therapy underwent per manent subcutaneous device implantation in the pilot study. The mean age of the patients was 6011 years (range, 46 to 72), with a mean weight of 99.012.0 kg (range, 87.0 to 114.0 [21826 lb; range, 192 to 251]). All the patients were men. The mean ejection fraction was 0.230.07 (range, 0.15 to 0.35). Five of the patients had coronary disease, and one had nonischemic cardiomyopa thy. Two had undergone previous cardiac surgery. One patient had a secondaryprevention indication, and five had a primaryprevention indication. All six patients underwent successful implan tation of the subcutaneous ICD, and in all the patients, defibrillation with 65J submaximal shocks was successful during two consecutive epi sodes of induced ventricular fibrillation. A total of 18 episodes of ventricular fibrillation were in duced (with one patient having multiple episodes of nonsustained ventricular fibrillation terminat ing before shock delivery); all the episodes were appropriately detected. After 4882 days of fol

Figure 3. Energy Delivered with the Subcutaneous Implantable CardioverterDefibrillator (ICD), According to Lead Configuration, and a Comparison of Defibrillation Thresholds in Transvenous and Subcutaneous ICDs. Panel A shows delivered defibrillation-threshold energies (measured in joules) in the four practical lead configurations that are described in Figure 1, as tested during trials of acute defibrillation ranges involving 78 patients. The T bars indicate standard deviations. Panel B shows a comparison of paired defibrillation-threshold data for transvenous ICDs and subcutaneous ICDs in 49 consecutive patients during randomized testing. The subcutaneous ICD was as effective as a transvenous ICD for terminating induced ventricular fibrillation, although with a significantly higher mean (SD) energy requirement (36.619.8 J vs. 11.18.5 J, P<0.001). In these tests, the transvenous ICD in one patient and the subcutaneous ICD in another patient failed to defibrillate induced ventricular fibrillation at maximum device output. In each of these two cases, 20 J was arbitrarily added to the highest energy tested to assign a defibrillation-threshold value. In the patient whose subcutaneous device failed defibrillation testing, the parasternal electrode had been incorrectly placed 6 cm lateral to the sternum.

lowup (95 patientmonths of subcutaneous ICD therapy), no spontaneous episodes of ventricular tachycardia or ventricular fibrillation had oc curred in the six patients, and all were well, with no devicerelated complications or inappropri ate shocks. Figure 4 shows data from one patient, with postoperative chest radiographs and an elec
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Figure 4. Chest Radiographs and an Electrocardiogram in a Patient Who Underwent Placement and Testing of a Subcutaneous Implantable CardioverterDefibrillator (ICD). The radiographs in Panels A and B show the locations of the electrode and pulse generator of a subcutaneous ICD in a 54-year-old man who was evaluated in the pilot study. Panel C shows an electrocardiogram of an episode of induced ventricular fibrillation and its termination in the patient. The subcutaneous ICD was being evaluated for primary prevention in the patient, who had coronary disease, New York Heart Association class II heart failure with an ejection fraction of 15%, and obstructive lung disease; the patients weight was 92 kg (203 lb).

trogram from one episode of induction and ter the first induction but not during the second in duction. As specified by the protocol, this patient mination of ventricular fibrillation. received a transvenous ICD. In another patient, it European Clinical Trial was necessary to reposition the electrode, which For the European singlegroup clinical trial, 65 pa was initially inserted in an inappropriate location tients who presented for ICD implantation satis 6 cm from the midline. The mean time to delivery fied the enrollment criteria. Eight patients declined of a shock was 14.02.5 seconds. The mean dura to participate in the study, and in two cases, the tion of the procedure, which was performed for patients physician opted for implantation of a the first time by most of the practitioners, includ transvenous ICD. Thus, 55 patients were enrolled ing device insertion and at least two induction in the trial, and all received a subcutaneous ICD. and termination tests, was 6733 minutes. The The clinical characteristics of the patients are procedure time was reduced to 5523 minutes for practitioners who completed at least three im shown in Table 1. Defibrillation testing was not possible in two plantations. patients because of intraoperative hemodynamic After 101 months and 46 patientyears of fol instability in one patient and failure to induce ven lowup, 54 of 55 patients (98%) were alive. One tricular fibrillation in the other. Therefore, 53 pa death from renal failure occurred 6 months after tients were evaluated for sensing and defibrillation device implantation in an 84yearold patient. during implantation. Of 137 episodes of induced Eighteen days before he died, the patient request ventricular fibrillation, 100% were detected by the ed that his subcutaneous ICD be turned off. subcutaneous ICD. In 52 of the 53 patients who A pocket infection developed in two patients; were tested (98%), two consecutive episodes of pocket revision was performed in one patient, and induced arrhythmia were successfully converted the other elected to discontinue defibrillator ther at 65 J. Among these 52 patients, conversion was apy. There were no cases of pocket erosion. No achieved with standard polarity in 50 patients and lead fractures developed in any patient, and no with reverse polarity in 2 patients. In the 53rd generator migration occurred. Minor lead migra patient, defibrillation at 65 J was achieved during tion was noted during followup in two patients.
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Another three patients had parasternal lead dis lodgement due to inadequate anchoring of the distal tip of the electrode. In each of these pa tients, lead repositioning was required within a week after surgery. In another patient, lead dis lodgement occurred at 6 months, during vigorous physical activity. In one patient, oversensing occurred because of inadequate placement of the electrode in the header block, resulting in inadequate contact with one of the sensing electrodes. This problem was addressed the day after surgery with reprogram ming of the detection vector rather than reopera tion. Inappropriate sensing due to muscle noise occurred in three patients; the problem was ad dressed with device reprogramming in all three cases. One patient who had received a new drug therapy had inappropriate sensing (double detec tion) after the narrow QRS complex in sinus rhythm changed to a right bundlebranch block during sinus tachycardia (150 beats per minute). During 3 months of further followup after the detection algorithm was revised, no inappropriate shocks occurred. No shocks were delivered inap propriately for atrial fibrillation, sinus tachycar dia, or supraventricular tachycardia at any time during the study when such episodes occurred at rates of more than 170 beats per minute. A total of 12 episodes of spontaneous ventricu lar tachycardia were detected and successfully treated in three patients, including 1 episode after the abovementioned software revisions (see the figure in the Supplementary Appendix). All patients were treated before the onset of syncope, and there were no adverse events. One of these patients was successfully treated for repetitive ven tricular tachycardia (VT storm), including seven successive episodes of ventricular tachycardia.

Table 1. Clinical Characteristics of 55 Patients in the European Clinical Trial of a Subcutaneous Implantable CardioverterDefibrillator (ICD).* Characteristic Age yr Mean Range Male sex no. (%) Body-mass index Mean Range Left ventricular ejection fraction Mean Range Cause of cardiac disease no. (%) Coronary artery disease Nonischemic cardiomyopathy Congenital heart disease Other condition Previous cardiac surgery no. (%) Indication for ICD no. (%) Primary prevention Secondary prevention 43 (78) 12 (22) 37 (67) 10 (18) 2 (4) 6 (11) 17 (31) 0.340.13 0.140.73 285 1740 5613 2284 44 (80) Value

* Plusminus values are means SD. The body-mass index is the weight in kilograms divided by the square of the height in meters.

Discussion
In the studies reported here, we describe the ini tial evaluation of an entirely subcutaneous ICD system. We identified a suitable device configura tion, assessed the defibrillation threshold of the device in comparison to that of the standard trans venous ICD, and conducted two small, single group trials of permanent device implantation. In the permanentimplantation studies, the sub cutaneous ICD successfully and consistently de tected and converted ventricular fibrillation that was induced during electrophysiological testing. The device also successfully detected and treated

12 episodes of spontaneous ventricular tachyar rhythmia that occurred in patients who were en rolled in the European clinical trial. The goal of developing a subcutaneous ICD was to overcome some of the problems that are as sociated with transvenous leads in conventional ICDs.3,6-11,14,15,40 Such a device could potentially reduce or eliminate problems such as failure to achieve vascular access, intravascular injury, and lead failure requiring difficult procedures for ex traction and replacement. Additional potential benefits of such a device include the preservation of venous access for other uses and the avoidance of radiation exposure during fluoroscopy, which is required for transvenous ICD implantation. These benefits would be especially important for young patients, in whom leads may fail during the decades that therapy is needed.41 The need for ICD systems that avoid the use of transvenous leads has been recognized previ ously,42-49 and some earlier exploratory efforts led to the present work.50,51 Some physicians have adapted existing technology to treat children with
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limited venous access. Leads have been inserted in unusual locations, and epicardial and subcuta neous leads have been used.44-46 Other subcuta neous defibrillation systems have been shown to work with an approximate tripling of the energy that is required by a transvenous system, find ings that are consistent with the results of our study.47,48 However, such systems have not incor porated subcutaneous rhythm detection but in stead have used transvenous or epicardial sensing electrodes for detection. Our studies are preliminary, earlyphase trials that were primarily intended to show the feasibil ity of an entirely subcutaneous ICD. They pro vide limited information regarding the detection and conversion of ventricular tachyarrhythmia in the clinical setting, despite the demonstration of consistent detection and termination of ventricu lar fibrillation at the time of implantation. These studies cannot show whether subcutaneous ICDs are superior to conventional transvenous ICDs with respect to such characteristics as lead sta bility or failure. Indeed, the initial experience in cludes several cases of problems such as lead migration, lead dislodgement, and inappropriate sensing. With respect to each of these issues, the subcutaneous ICD system was adjusted shortly af ter implantation in an effort to improve the sys tems reliability. Problems with lead dislodgment have led to the introduction of an anchoring sleeve and a new surgical technique. Inappropri ate sensing has been addressed through software

revision, with no incidents in the 3 months after revision. However, these modifications will require further testing in additional groups of patients. Ultimately, the relative benefit of subcutaneous ICDs, as compared with transvenous ICDs, will need to be shown in large, longterm, random ized, prospective, multicenter clinical trials. In addition, there are inherent limitations of this device design. Although transient postshock pacing is available, the subcutaneous ICD cannot provide longterm pacing. It is therefore not an alternative to transvenous ICDs when antibrady cardia pacing is required. Also, the subcutaneous ICD is not designed to treat patients with ventricu lar tachycardia at rates slower than 170 beats per minute. The lack of capability to provide anti tachycardia pacing may be a limitation in patients with frequent, recurrent, monomorphic ventricu lar tachycardia. In conclusion, we found that in small, nonran domized studies, an entirely subcutaneous ICD system successfully and consistently detected and converted episodes of ventricular fibrillation that were induced during electrophysiological testing. It also successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia.
Supported by Cameron Health. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank Jon Hunt, Ph.D., Linda Smith, B.A., Jay Warren, M.S.E.E., Stephen OConnor, Ph.D., Rick Sanghera, B.S.E.E., Jill An derson, B.S.N., and George Johnson, B.S.E.E., for their assistance.

Appendix The authors affiliations are as follows: the Seattle Institute for Cardiac Research, Seattle (G.H.B.); Auckland City Hospital, Auckland (W.M.S., M.A.H.); and Christchurch Hospital, Christchurch (I.G.C., I.C.M., R.E.P.) both in New Zealand; Liverpool Heart and Chest Hospital, Liverpool (D.J.W.); Glasgow Royal Infirmary, Glasgow (D.T.C.); Kings College Hospital, London (F.D.M.); the Departments of Cardiology (S.P.F., A.A.G.) and Anaesthetics and Intensive Care (A.O.), Papworth Hospital, Cambridge; Russells Hall Hospital, Dudley (C.S.B.); and the School of Biological Sciences, University of Cambridge, Cambridge (A.A.G.) all in the United Kingdom; Burdenko Hospital, Moscow (A.V.A.); I.R.C.C.S. Istituto Policlinico San Donato, Milan (P.L., R.C.); KerckhoffKlinik, Bad Nauheim (J.S.); Akade mische Lehrpraxisklinik der TU Dresden, Dresden (S.G.S.); and Klinikum Kassel, Kassel (J.N.) all in Germany; and Erasmus Medical Center, Rotterdam (L.J., D.T.); St. Antonius Hospital, Nieuwegein (L.B.); University Medical Center Groningen, University of Gronin gen, Groningen (A.H.M., I.C.V.G.); and Academic Medical Center, Amsterdam (A.A.W., P.F.D, R.E.K.) all in the Netherlands. References able Defibrillators (AVID) Investigators. A comparison of antiarrhythmicdrug therapy with implantable defibrillators in patients resuscitated from nearfatal ven tricular arrhythmias. N Engl J Med 1997; 337:157683. 2. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrilla tor in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:87783.
1. The Antiarrhythmics versus Implant 3. Bardy GH, Lee KL, Mark DB, et al.

Amiodarone or an implantable cardiovert erdefibrillator for congestive heart fail ure. N Engl J Med 2005;352:22537. [Erra tum, N Engl J Med 2005;352:2146.] 4. Myerburg RJ. Implantable cardiovert erdefibrillators after myocardial infarc tion. N Engl J Med 2008;359:224553. 5. Epstein AE. Benefits of the implant able cardioverterdefibrillator. J Am Coll Cardiol 2008;52:11227. 6. Grimm W, Menz V, Hoffmann J, et al.

Complications of thirdgeneration implant able cardioverter defibrillator therapy. Pac ing Clin Electrophysiol 1999;22:20611. 7. van Rooden CJ, Molhoek SG, Rosend aal FR, Schalij MJ, Meinders AE, Huisman MV. Incidence and risk factors of early ve nous thrombosis associated with perma nent pacemaker leads. J Cardiovasc Elec trophysiol 2004;15:125862. 8. Alter P, Waldhans S, Plachta E, Moos dorf R, Grimm W. Complications of im plantable cardioverter defibrillator thera

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